The Fetal Environment and the Development of Hypertension-The Epigenetic Modification by Glucocorticoids.

Intrauterine growth restriction (IUGR) is a risk factor for postnatal cardiovascular, metabolic, and psychiatric disorders. In most IUGR models, placental dysfunction that causes reduced 11β-hydroxysteroid dehydrogenase 2 (11βHSD2) activity, which degrades glucocorticoids (GCs) in the placenta, resulting in fetal GC overexposure. This overexposure to GCs continues to affect not only intrauterine fetal development itself, but also the metabolic status and neural activity in adulthood through epigenetic changes such as microRNA change, histone modification, and DNA methylation.

Recent advances in biomarkers for senescence: Bridging basic research to clinic.

In this review, we review the current status of biomarkers for aging and possible perspectives on anti-aging or rejuvenation from the standpoint of biomarkers. Aging is observed in all cells and organs, and we focused on research into senescence in the skin, musculoskeletal system, immune system, and cardiovascular system. Commonly used biomarkers include SA-βgal, cell-cycle markers, senescence-associated secretory phenotype (SASP) factors, damage-associated molecular patterns (DAMPs), and DNA-damage-related markers.

Hypoxia Modulates Sodium Chloride Co-transporter via CaMKII-β Pathway: An In Vitro Study with mDCT15 Cells.

Background: Hypoxia plays a crucial role in regulating various cellular functions, including ion-transport mechanisms in the kidney. The sodium-chloride co-transporter (NCC) is essential for sodium reabsorption in the distal convoluted tubule (DCT). However, the effects of hypoxia on NCC expression and its regulatory pathways remain unclear.

Home blood pressure-lowering effect of esaxerenone versus trichlormethiazide for uncontrolled hypertension: a predefined subanalysis of the EXCITE-HT randomized controlled trial by basal calcium channel blocker versus angiotensin receptor blocker.

This prespecified subanalysis of the multicenter, randomized, open-label, parallel-group EXCITE-HT study aimed to examine the non-inferiority of esaxerenone to trichlormethiazide as a second-line antihypertensive agent according to the basal antihypertensive agent used (angiotensin receptor blocker [ARB] or calcium channel blocker [CCB]). The primary endpoint, change in morning home systolic/diastolic blood pressure (SBP/DBP) from baseline to end of treatment was similar between the two groups (intergroup difference in least squares mean change [95% confidence interval]: -1.3 [-3.

Esaxerenone Attenuates Aldosterone-Induced Mitochondrial Damage-Mediated Pyroptosis in Mouse Aorta and Rat Vascular Smooth Muscle Cells.

Background: Vascular smooth muscle cell (VSMC) injury caused by the inflammatory response plays a key role in cardiovascular disease (CVD), and the vasoprotective effects of mineralocorticoid receptor blockers (MRBs) support the role of mineralocorticoid receptor (MR) activation.

Methods: C57BL/6 mice and VSMCs isolated from rats were treated with aldosterone and esaxerenone. Caspase-1, GSDMD-N, IL-1β, and NR3C2 expression and DNA damage in aortic VSMCs were detected using immunohistochemistry, Western blotting, and TUNEL staining.

Home blood pressure-lowering effect of a non-steroidal mineralocorticoid receptor blocker, esaxerenone, versus trichlormethiazide for uncontrolled hypertension: the EXCITE-HT randomized controlled study.

The EXCITE-HT study aimed to evaluate the efficacy and safety of esaxerenone versus thiazide diuretics (trichlormethiazide) as second-line treatment for Japanese patients with uncontrolled essential hypertension. This was a 12-week, multicenter, randomized, open-label, parallel-group study. The non-inferiority of esaxerenone to trichlormethiazide was confirmed if the upper limit of the two-sided 95% confidence interval (CI) for the difference in systolic blood pressure (SBP)/diastolic blood pressure (DBP) change between groups was below 3.

Regulating distal nephron functions and salt sensitivity.

This review highlights the molecular basis of salt sensitivity in hypertension, with a focus on the regulation of sodium transport in the distal nephron. Sodium reabsorption in this region is often linked to the actions of aldosterone, although in recent years numerous findings have been reported on the aldosterone-independent pathway of acquiring salt sensitivity by potassium deficiency or potassium loading. The key to this discussion is the interplay, through extracellular potassium concentration, between the first part of the tubules expressing the Na-Cl cotransporter (NCC) and the second part expressing the epithelial Na channel (ENaC).

Esaxerenone Inhibits Interferon-γ Induced Pyroptosis of Macrophages in the Lungs of Aldosterone-treated Mice.

Lung immune cells such as lymphocytes and macrophages can induce an inflammatory response due to the activation of mineralocorticoid receptor (MR), which is manifested by the infiltration of inflammatory cells and the secretion of inflammatory cytokines and subsequent apoptosis, pyroptosis and necrosis of intrinsic lung cells and immune cells. Macrophages are immune cells that are abundant in the lung and act as the first line of defense against pathogens but are also aggravating factors of infection. The activation of the renin-angiotensin-aldosterone system (RAAS), especially aldosterone-stimulated MR activation, can induce macrophage and CD8 T cell aggregation and the secretion of cytokines such as tumor necrosis factor-α (TNF-α) and interferon-gamma (IFN-γ).

Eplerenone reduces lymphangiogenesis in the contralateral kidneys of UUO rats.

Inflammation and fibrosis often occur in the kidney after acute injury, resulting in chronic kidney disease and consequent renal failure. Recent studies have indicated that lymphangiogenesis can drive renal inflammation and fibrosis in injured kidneys. However, whether and how this pathogenesis affects the contralateral kidney remain largely unknown.

Exploratory study on the relationship between urinary sodium/potassium ratio, salt intake, and the antihypertensive effect of esaxerenone: the ENaK Study.

Excessive salt intake is one of the causes of hypertension, and reducing salt intake is important for managing the risk of hypertension and subsequent cardiovascular events. Esaxerenone, a mineralocorticoid receptor blocker, has the potential to exert an antihypertensive effect in hypertensive patients with excessive salt intake, but evidence is still lacking, especially in clinical settings. We aimed to determine if baseline sodium/potassium ratio and baseline estimated 24-h urinary sodium excretion can predict the antihypertensive effect of esaxerenone in patients with essential hypertension inadequately controlled with an angiotensin receptor blocker (ARB) or a calcium channel blocker (CCB).

Development of a plasma maltose assay method as a screening test for upper gastrointestinal disorders.

Background And Objective: The disaccharide loading test is a method to assess gastric mucosal damage. Since Trelan-G75, which is used for the sugar tolerance test, contains disaccharide maltose, if maltose is detected at a high sensitivity in the sample blood used in the sugar tolerance test, screening for upper gastrointestinal mucosal damage can be made simultaneously with the sugar tolerance test for the diagnosis of diabetes.

Methods: Glucose-6-phosphate is generated by treating maltose with maltose phosphorylase, β-phosphoglucomutase, and glucose-1,6-bisphosphate.

Rationale and design of a multicenter randomized study comparing the efficacy and safety of esaxerenone versus trichlormethiazide in patients with uncontrolled essential hypertension: EXCITE-HT study.

The next-generation mineralocorticoid receptor blocker (MRB) esaxerenone has favorable antihypertensive effects in patients who do not respond to treatment with first-line antihypertensive agents and may be beneficial as a second-line treatment. However, MRBs are currently considered a fourth-line treatment as there is no clinical evidence comparing the efficacy of esaxerenone with other classes of antihypertensive agents. The multicenter, randomized, open-label, parallel-group EXCITE-HT study will evaluate the efficacy and safety of esaxerenone as a second-line agent in the treatment of Japanese patients with uncontrolled essential hypertension.

Esaxerenone Inhibits Renal Angiogenesis and Endothelial-Mesenchymal Transition via the VEGFA and TGF-β1 Pathways in Aldosterone-Infused Mice.

Renal fibrosis is an inevitable process in the progression of chronic kidney disease (CKD). Angiogenesis plays an important role in this process. Vascular endothelial cells are involved in renal fibrosis by phenotypic transformation and secretion of extracellular matrix.

Sex differences in the evaluation of proteinuria using the urine dipstick test.

Background: The urine protein dipstick test is widely used, but false-positive and false-negative results may occur. This study aimed to compare the urine protein dipstick test with a urine protein quantification method.

Methods: The data were extracted using the Abbott Diagnostic Support System, which analyzes the inspection results using multiple parameters.

NGAL is a Novel Target in Hypertension by Modulating the NCC-Mediated Renal Na Balance.

Background: The expression of NGAL/lcn2 (neutrophil gelatinase-associated lipocalin) is directly modulated by mineralocorticoid receptor activation but its role in blood pressure control is unclear.

Methods: a potential relationship between NGAL plasma levels, systolic blood pressure and urinary Na excretion was assessed in the STANISLAS cohort. The specific role of NGAL/lcn2 in salt-sensitive hypertension was studied using lcn2-knockout mice (lcn2 KO) fed with low-Na diet (0Na).

Variation in antibody titers determined by Abbott and Roche Elecsys SARS-CoV-2 assays in vaccinated healthcare workers.

SARS-CoV-2-specific antibody measurement is important for evaluating COVID-19 vaccine efficacy. We quantified and compared anti-spike (S) antibodies using different commercial immunoassays. We tested serum samples from 70 SARS-CoV-2-naive health care workers 2 weeks after vaccination with a single dose of BNT162b2, 2 and 4 weeks, and 3 months after the second dose of BNT162b2.

How animal models can be utilized to find new biomarkers for cardiovascular diseases.

It has been more than 60 years since the colonized genetic model of hypertension was first established. Model animals contribute greatly to the advance of understanding of the pathophysiology and development of effective therapy. In this review, the author focuses on two points: gene-related biomarkers and the use of humanized mice to search for biomarkers.

Quality is not an act, it is a habit-Aristotle.

To measure blood pressure precisely and make the data comparable among facilities, measurement methods and devices must be standardized. Since the Minamata Convention on Mercury, there is no metrological standard for sphygmomanometers. The current validation methods recommended by non-profit organizations in Japan, the US, and European Union countries are not necessarily applicable to the clinical setting, and no protocol for daily or routine performance of quality control has been defined.

Eplerenone inhibits the macrophage-to-myofibroblast transition in rats with UUO-induced type 4 cardiorenal syndrome through the MR/CTGF pathway.

Cardiovascular complications are the leading causes of death in patients with chronic kidney disease (CKD), accounting for approximately 50% of deaths. Despite significant advances in the understanding of cardiac disease due to CKD, the underlying mechanisms involved in many pathological changes have not been fully elucidated. In our previous study, we observed severe fibrosis in the contralateral kidney of a 6-month-old rat UUO model.